Skip to main content

Advertisement

Log in

Effect of Ag-1031 on apoptosis in gastric cancer AGS cells and its effects on the PI3K/AKT/mTOR signaling pathway

  • Original Research Paper
  • Published:
Biotechnology Letters Aims and scope Submit manuscript

Abstract

Purpose

To investigate the effect of Ag-1031 on apoptosis of gastric cancer AGS cells and the PI3K/AKT/mTOR signaling pathway.

Methods

Gastric cancer cells were treated with different doses of Ag-1031. Cell viability was determined with MTT assay. Apoptosis was analyzed with Hoechst 33342 staining and Annexin V-FITC/PI double staining. The protein expression levels of p-PI3K, p-AKT, p-mTOR, PI3K, AKT and mTOR were assayed with western blotting method.

Results

Different doses of Ag-1031 significantly inhibited the proliferation of AGS cells. Moreover, Ag-1031 induced apoptosis,in gastric cancer cells. In addition, Ag-1031 significantly and dose-dependently inhibited the protein expressions of p-PI3K, p-AKT and p-mTOR. However, it had no effect on the protein expressions of PI3K, AKT and mTOR.

Conclusion

In this study, it was found for the first time that Ag-1031 exerts an anti-tumor effect by induction apoptosis in gastric cancer AGS cells, through a mechanism related to inhibition of the activation of the PI3K/AKT/mTOR signaling pathway.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig.2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  • Altman AM, Mahmud J, Nikolovska-Coleska Z, Chan G (2019) HCMV modulation of cellular PI3K/AKT/mTOR signaling: new opportunities for therapeutic intervention? Antiviral Res 163:82–90

    Article  CAS  Google Scholar 

  • Belloc F, Dumain P, Boisseau MR, Jalloustre C, Reiffers J, Bernard P (1994) A flow cytometric method using Hoechst 33342 and propidium iodide for simultaneous cell cycle analysis and apoptosis determination in unfixed cells. Cytometry 17:59–65

    Article  CAS  Google Scholar 

  • Beyer K, Baukloh AK, Stoyanova A, Kamphues C, Sattler A, Kotsch K (2019) Interactions of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) with the immune system: implications for inflammation and cancer. Cancers (Basel) 11:1–9

    Google Scholar 

  • Chen L, Du C, Wang L, Yang C, Zhang JR, Li N et al (2014) Human positive coactivator 4 (PC4) is involved in the progression and prognosis of astrocytoma. J Neurol Sci 346:293–298

    Article  CAS  Google Scholar 

  • Corti F, Nichetti F, Raimondi A, Niger M, Prinzi N, Torchio M et al (2019) Targeting the PI3K/AKT/mTOR pathway in biliary tract cancers: a review of current evidences and future perspectives. Cancer Treat Rev 72:45–55

    Article  CAS  Google Scholar 

  • Dong Q, Yuan Z, Zhang B, Meng M, Zhuang H (2014) Human positive cofactor 4 (PC4) is a promising target to improve the radiation therapy effect of esophageal squamous cell carcinomas. Int J Radiat Oncol 90:803–811

    Article  Google Scholar 

  • Elmore S (2007) Apoptosis: a review of programmed cell death. Toxicol Pathol 35:495–516

    Article  CAS  Google Scholar 

  • Fu J, Zhang H, Zhang Y, Zhang T (2019) AG1031 induces apoptosis through suppressing SIRT1/p53 pathway in human neuroblastoma cells. Mol Cell Biochem 454:165–175

    Article  CAS  Google Scholar 

  • Hassanalilou T, Ghavamzadeh S, Khalili L (2019) Curcumin and gastric cancer: a review on mechanisms of action. J Gastrointest Cancer 50:185–192

    Article  Google Scholar 

  • Hu X, Zhang C, Zhang Y, Hong CS, Chen W, Shen W et al (2017) Down regulation of human positive coactivator 4 suppress tumorigenesis and lung metastasis of osteosarcoma. Oncotarget 8:53210–53225

    Article  Google Scholar 

  • Jingxuan F, Zhang H, Zhang Y, Zhang T (2019) AG1031 induces apoptosis through suppressing SIRT1/p53 pathway in human neuroblastoma cells. Mol Cell Biochem 454(1–2):165–175

    Google Scholar 

  • Kadokawa Y, Sonoda K, Nakajima S, Kawabe A, Egawa H (2010) Advanced gastric cancer in an elderly woman showing histopathologic CR after a course of S-1 and CDDP combination therapy. Gan To Kagaku Ryoho 37:711–713

    PubMed  Google Scholar 

  • Lee HJ, Saralamma VVG, Kim SM (2018) Pectolinarigenin induced cell cycle arrest, autophagy, and apoptosis in gastric cancer cell via PI3K/AKT/mTOR signaling pathway. Nutrients 10:1043

    Article  Google Scholar 

  • Li H, He C, Wang X, Wang H, Nan G, Fang L (2019) MicroRNA-183 affects the development of gastric cancer by regulating autophagy via MALAT1-miR-183-SIRT1 axis and PI3K/AKT/mTOR signals. Artif Cells Nanomed Biotechnol 47:3163–3171

    Article  CAS  Google Scholar 

  • Pistritto G, Trisciuoglio D, Ceci C, Garufi A, D'Orazi G (2016) Apoptosis as anticancer mechanism: function and dysfunction of its modulators and targeted therapeutic strategies. Aging (Albany NY) 8:603–619

    Article  CAS  Google Scholar 

  • Ravanan P, Srikumar IF, Talwar P (2017) Autophagy: the spotlight for cellular stress responses. Life Sci 188:53–67

    Article  CAS  Google Scholar 

  • Riquelme I, Tapia O, Espinoza JA, Leal P, Buchegger K, Sandoval A et al (2016) The gene expression status of the PI3K/AKT/mTOR pathway in gastric cancer tissues and cell lines. Pathol Oncol Res 22:797–805

    Article  CAS  Google Scholar 

  • Sun HX, Xu YC, Chen XW (2017) Expression of proteins associated with PI3K/AKT/mTOR signaling pathway in gastric cancer tissues. Chin J Public Health 10:1455–1458

    Google Scholar 

  • Wang Z, Zhou L, Zheng X, Chen G, Pan R, Li J et al (2017) Autophagy protects against PI3K/Akt/mTOR-mediated apoptosis of spinal cord neurons after mechanical injury. Neurosci Lett 656:158–164

    Article  CAS  Google Scholar 

  • Wang Y, Wang H, Ge H, Yang Z (2018a) AG-1031 induced autophagic cell death and apoptosis in C6 glioma cells associated with Notch-1 signaling pathway. J Cell Biochem 119:5893–5903

    Article  CAS  Google Scholar 

  • Wang X, Jiao X, Meng Y, Chen H, Griffin N, Gao X et al (2018b) Methionine enkephalin (MENK) inhibits human gastric cancer through regulating tumor associated macrophages (TAMs) and PI3K/AKT/mTOR signaling pathway inside cancer cells. Int Immunopharmacol 65:312–322

    Article  CAS  Google Scholar 

  • Xie JQ, Ren QC (2016) Research progress of transcription auxiliary factor PC4 in tumor. J Luzhou Med College 39:491–494

    Google Scholar 

  • Yang ZX (2019) Trend and prediction of stomach cancer incidence in China. China Cancer 28:321–326

    Google Scholar 

  • Zeng L, Liao Q, Zou Z, Wen Y, Wang J, Liu C et al (2018) Long Non-Coding RNA XLOC_006753 promotes the development of multidrug resistance in gastric cancer cells through the PI3K/AKT/mTOR signaling pathway. Cell Physiol Biochem 51:1221–1236

    Article  CAS  Google Scholar 

  • Zhang K, Liu W, Qu Z, Liu Q, Chen J, Tao R et al (2019) In vitro and in vivo human gastric cancer inhibition by Trifolirhizin is facilitated via autophagy, mitochondrial mediated programmed cell death, G2/M phase cell cycle arrest and inhibition of m-TOR/PI3K/AKT signalling pathway. J BUON 24:1100–1105

    PubMed  Google Scholar 

Download references

Acknowledgements

The work was supported by Provincial Quality Engineering Project of colleges and universities in Anhui Province (2019xfxm90).

Author information

Authors and Affiliations

Authors

Contributions

This study was done by the authors named in this article and the authors accept all liabilities resulting from claims which relate to this article and its contents. The study was conceived and designed by JD; DL, LC, LS collected and analyzed the data. JD wrote the manuscript. All authors read and approved the manuscript prior to publication.

Corresponding author

Correspondence to LiXia Sun.

Ethics declarations

Conflict of interest

There are no conflicts of interest in this study.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Dai, J., Liu, D., Chen, L. et al. Effect of Ag-1031 on apoptosis in gastric cancer AGS cells and its effects on the PI3K/AKT/mTOR signaling pathway. Biotechnol Lett 42, 2447–2452 (2020). https://doi.org/10.1007/s10529-020-02954-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10529-020-02954-6

Keywords

Navigation